My Comment

Why this study – the rationale/objective?

Acute kidney injury associated with the administration of iodinated-contrast material during angiography can result in severe renal function deterioration, need for dialysis or death. Peri-procedural administration of saline is considered the standard of care to prevent this complication. Yet, in clinical practice, alternative/additional treatments for the prevention of contrast-associated acute kidney injury, as intravenous sodium bicarbonate or N-acetylcysteine, are widely used on the basis of the hypotheses that urinary alkalinization and scavenging of reactive oxygen species mitigate renal tubular epithelial-cell injury. Nevertheless, prior trials comparing sodium bicarbonate or N-acetylcysteine to standard treatment have provided inconsistent results.

How was it executed – the methodology?

In the Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial, a total of 5,177 patients at high risk of contrast-induced renal failure (eGFR 15 to 44.9 ml/min per 1.73m2), scheduled to undergo angiography, were enrolled and randomized in a 2-by-2 factorial fashion. The first randomized interventional treatment compared intravenous 1.26% sodium bicarbonate vs. 0.9% sodium chloride, while the second tested treatment compared oral N-acetylcysteine 1200 mg vs. placebo twice daily for 4 days after angiography. The primary endpoint was the occurrence of a composite of death, need for dialysis or persistent increase ≥50% of serum creatinine at 90 days after angiography. A modified intention-to-treat analysis was used for the interpretation of the primary study result, and included all randomized patients who have effectively received the assigned interventions.

What is the main result?

PRESERVE trial was stopped prematurely for futility after a pre-specified interim analysis. The median eGFR was 50.2 ml/min per 1.73 m2 and the median volume of contrast administered was 85 ml. There was no difference for the primary endpoint of death, need for dialysis or persistent increase of creatinine at 90 days between the intravenous treatment with sodium bicarbonate vs. sodium chloride (4.4% vs. 4.7%; OR 0.93 95%CI 0.72-1.22; p= 0.62) nor, between the second randomized treatment of N-acetilcysteine vs. placebo (4.6% vs. 4.5%; OR 1.02 95%CI 0.78-1.33; p= 0.88).

Critical reading and the relevance for clinical practice

The PRESERVE trial provide compelling evidence of a lack of benefit for a treatment with sodium bicarbonate or N-acetylcysteine for the prevention of death or kidney injury in patients with impaired renal function undergoing coronary or non-conorary angiography. Among the strengths of this trial, there was the selection of an at least moderate risk population. Yet, the total amount of contrast used during angiography was low, and only 28.5% of patients underwent PCI. This may justify the lower event rate and a possible underestimation of the treatment efficacy. Despite subgroup analysis for higher contrast volume (i.e. >125 ml) was consistent with the main study results, further evaluation of the subgroups based on the contrast volume/eGFR ratio might provide further detail.